Anti-cancer agents in medicinal chemistry最新文献

{"title":"Arsenic Trioxide Suppresses Angiogenesis in Non-small Cell Lung Cancer <i>via</i> the Nrf2-IL-33 Signaling Pathway.","authors":"Mingdong Wang, Jizhong Yin, Qianyu Han, Bing Li, Xue-Wei Zhao, Lei Xue","doi":"10.2174/0118715206288348240420174853","DOIUrl":"10.2174/0118715206288348240420174853","url":null,"abstract":"<p><strong>Background: </strong>Non-Small Cell Lung Cancer (NSCLC) ranks as a leading cause of cancer-related mortality, necessitating the urgent search for cost-effective and efficient anti-NSCLC drugs. Our preliminary research has demonstrated that arsenic trioxide (ATO) significantly inhibits NSCLC angiogenesis, exerting anti-tumor effects. In conjunction with existing literature reports, the Nrf2-IL-33 pathway is emerging as a novel mechanism in NSCLC angiogenesis.</p><p><strong>Objective: </strong>This study aimed to elucidate whether ATO can inhibit NSCLC angiogenesis through the Nrf2-IL-33 pathway.</p><p><strong>Methods: </strong>Immunohistochemistry was employed to assess the expression of Nrf2, IL-33, and CD31 in tumor tissues from patients with NSCLC. DETA-NONOate was used as a nitric oxide (NO) donor to mimic high levels of NO in the tumor microenvironment. Western blot, quantitative real-time PCR, and enzyme-linked immunosorbent assay were utilized to evaluate the expression of Nrf2 and IL-33 in the NCI-H1299 cell line. Subcutaneous xenograft models were established in nude mice by implanting NCI-H1299 cells to assess the anti-tumor efficacy of ATO.</p><p><strong>Results: </strong>High expression levels of Nrf2 and IL-33 were observed in tumor samples from patients with NSCLC, and Nrf2 expression positively correlated with microvascular density in NSCLC. <i>In vitro</i>, NO (released from 1mM DETA-NONOate) promoted activation of the Nrf2-IL-33 signaling pathway in NCI-H1299 cells, which was reversed by ATO. Additionally, both Nrf2 deficiency and ATO treatment significantly attenuated NOinduced IL-33 expression. <i>In vivo</i>, both ATO and the Nrf2 inhibitor ML385 demonstrated significant inhibitory effects on angiogenesis tumor growth.</p><p><strong>Conclusion: </strong>Nrf2-IL-33 signaling is usually activated in NSCLC and positively correlates with tumor angiogenesis. ATO effectively disrupts the activation of the Nrf2-IL-33 pathway in NSCLC and thus inhibits angiogenesis, suggesting its potential as an anti-angiogenic agent for use in the treatment of NSCLC.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"1142-1150"},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Antheraea proylei</i> J. Sericin Induces Apoptosis in a Caspase-dependent Manner in A549 and HeLa Cells.","authors":"Potsangbam Jolly Devi, Asem Robinson Singh, Naorem Tarundas Singh, Laishram Rupachandra Singh, Sanjenbam Kunjeshwori Devi, Lisam Shanjukumar Singh","doi":"10.2174/1871520623666230329123437","DOIUrl":"10.2174/1871520623666230329123437","url":null,"abstract":"<p><strong>Background: </strong>In spite of much progress in cancer, the global cancer burden is still significant and increasing. Sericin, an adhesive protein of silk cocoons, has been shown to be a potential protein in various biomedical applications, including cancer therapeutics. The present study evaluates the anticancer property of sericin from cocoons of <i>Antheraea proylei</i> J (SAP) against human lung cancer (A549) and cervical cancer (HeLa) cell lines. This is the first report of anti-cancer activity of the non-mulberry silkworm <i>A. proylei</i> J.</p><p><strong>Objective: </strong>Establish the antiproliferative potential of SAP. 2. Identify the molecular mechanism of cell death induced by SAP on two different cell lines.</p><p><strong>Aims: </strong>To investigate the anticancer activity of sericin preparation from cocoons of <i>A. proylei</i>.</p><p><strong>Methods: </strong>SAP was prepared from cocoons of <i>A. proylei</i> J. by the process of the degumming method. Cytotoxic activity was assessed by MTT assay, and genotoxicity was assessed by comet assay. Cleavage of caspase and PARP proteins and phosphorylation of MAPK pathway members were analysed by Western blotting. Cell cycle analysis was done by flow cytometer.</p><p><strong>Results: </strong>SAP causes cytotoxicity to A549 and HeLa cell lines with the IC₅₀ values 3.8 and 3.9 μg/μl respectively. SAP induces apoptosis in a dose-dependent manner through caspase-3 and p38, MAPK pathways in A549 and HeLa cells. Moreover, in A549 and HeLa cells, SAP induces cell cycle arrest at the S phase in a dose-dependent manner.</p><p><strong>Conclusion: </strong>The difference in the molecular mechanisms of apoptosis induced by SAP in A549 and HeLa cell lines may be due to the difference in the genotypes of the cancer cell lines. However, further investigation is warranted. The overall results of the present study envisage the possibility of using SAP as an anti-tumorigenic agent.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"709-717"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9222866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-proliferative, Morphological and Molecular Docking Studies of New Thiophene Derivatives and their Strategy in Ionic Liquids Immobilized Reactions.","authors":"Rafat M Mohareb, Sayeed Mukhtar, Humaira Parveen, Mahmoud A Abdelaziz, Ensaf S Alwan","doi":"10.2174/0118715206262307231122104748","DOIUrl":"10.2174/0118715206262307231122104748","url":null,"abstract":"<p><strong>Background: </strong>A number of research were conducted on the pyran and thiophene derivatives, which were attributed to have a wide range of biological activities, including anti-plasmodial, as well as acting as caspase, hepatitis C and cancer inhibitors.</p><p><strong>Objective: </strong>The multicomponent reactions of the 5-acetyl-2-amino-4-(phenylamino)-thiophene-3-carbonitrile produced biologically active target molecules like pyran and their fused derivatives. Comparison between regular catalytic multi-component reactions and solvent-free ionic liquids immobilized multicomponent was studied.</p><p><strong>Methods: </strong>The multicomponent reactions in this work were carried out not only under the reflux conditions using triethylamine as a catalyst but also in solvent-free ionic liquids immobilized magnetic nanoparticles (MNPs) catalysts.</p><p><strong>Results: </strong>Through this work, thirty-one new compounds were synthesized and characterized and were evaluated toward the six cancer cell lines, namely A549, HT-29, MKN-45, U87MG, and SMMC-7721 and H460. The most active compounds were further screened toward seventeen cancer cell lines classified according to the disease. In addition, the effect of compound 11e on the A549 cell line was selected to make further morphological changes in the cell line. The Molecular docking studies of 11e and 11f were carried and promising results were obtained.</p><p><strong>Conclusion: </strong>The synthesis of heterocyclic compounds derived from thiophene derivatives has been receiving significant attention. After a detailed optimizing study, it has been found that the solvent-free ionic liquids immobilized multi-component syntheses afforded a high yield of compounds, opening a greener procedure for this synthetically relevant transformation. Many of the synthesized compounds can be considered anticancer agents, enhancing further studies.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"691-708"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139696833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Novel EGFR Inhibitors for the Targeted Therapy of Colorectal Cancer Using Pharmacophore Modelling, Docking, Molecular Dynamic Simulation and Biological Activity Prediction.","authors":"Amrutha Krishnan K, Sudha George Valavi, Amitha Joy","doi":"10.2174/0118715206275566231206094645","DOIUrl":"10.2174/0118715206275566231206094645","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is considered the second deadliest cancer in the world. One of the reasons for the occurrence of this cancer is the deregulation of the Epidermal Growth Factor Receptor (EGFR), which plays a critical role in regulating cell division, persistence, differentiation, and migration. The overexpression of the EGFR protein leads to its dysregulation and causes CRC.</p><p><strong>Objectives: </strong>Hence, this work aims to identify and validate novel EGFR inhibitors for the treatment of colorectal cancer employing various computer aided techniques such as pharmacophore modeling, docking, molecular dynamic simulation and Quantitative Structure-Activity Relationship (QSAR) analysis.</p><p><strong>Methods: </strong>In this work, a shared-featured ligand-based pharmacophore model was generated using the known inhibitors of EGFR. The best model was validated and screened against ZincPharmer and Maybridge databases, and 143 hits were obtained. Pharmacokinetic and toxicological properties of these hits were studied, and the acceptable ligands were docked against EGFR. The best five protein-ligand complexes with binding energy less than -5 kcal/mol were selected. The molecular dynamic simulation studies of these complexes were conducted for 100 nanoseconds (ns), and the results were analyzed. The biological activity of this ligand was calculated using QSAR analysis.</p><p><strong>Results: </strong>The best complex with Root Mean Square Deviation (RMSD) 3.429 Å and Radius of Gyration (RoG) 20.181 Å was selected. The Root Mean Square Fluctuations (RMSF) results were also found to be satisfactory. The biological activity of this ligand was found to be 1.38 μM.</p><p><strong>Conclusion: </strong>This work hereby proposes the ligand 2-((1,6-dimethyl-4-oxo-1,4-dihydropyridin-3-yl)oxy)-N- (1H-indol-4-yl)acetamide as a potential EGFR inhibitor for the treatment of colorectal cancer. The wet lab analysis must be conducted, however, to confirm this hypothesis.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"263-279"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139085571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coumarin-derived Hydroxamic Acids as Histone Deacetylase Inhibitors: A Review of Anti-cancer Activities.","authors":"Nguyen Quang Khai, Tran Khac Vu","doi":"10.2174/0118715206272112231102063919","DOIUrl":"10.2174/0118715206272112231102063919","url":null,"abstract":"<p><p>Since coumarin and hydroxamic acid compounds are well-known in medicinal chemistry, a variety of their derivatives have been highlighted due to their potential uses for plentiful treatments. Different compounds of their derivatives acting through diverse activities, such as anti-tumor, anti-cancer, anti-inflammation, and histone deacetylase inhibition, have been comprehensively investigated by many researchers over the years. This present review provides the latest literature and knowledge on hydroxamic acids derived from coumarin. Overall, some recent advancements in biological activities of hybrid derivatives of hydroxamic acids containing coumarin moieties in medicinal chemistry are discussed.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"18-29"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92152293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and Synthesis of Aspirin-chalcone Mimic Conjugates as Potential Anticancer Agents.","authors":"Reham A Mohamed-Ezzat, Aladdin M Srour","doi":"10.2174/0118715206280025231213065519","DOIUrl":"10.2174/0118715206280025231213065519","url":null,"abstract":"<p><strong>Background: </strong>Extensive research has been conducted on aspirin, a widely recognized NSAID medication, regarding its potential as an anticancer agent. Studies have revealed its ability to trigger cell death in different types of cancer cells.</p><p><strong>Methods: </strong>A set of aspirin-chalcone mimic conjugates 5a-k and 6a-d utilizing the freshly prepared acid chloride of aspirin moiety has been designed and synthesized. To evaluate the newly developed compounds, the NCI 60- cell line panel was employed to assess their anti-proliferative properties. Subsequently, cell cycle analysis was conducted along with an examination of the compounds' impact on the levels of p53, Bax, Bcl-2, active caspase- 3, and their inhibition mechanism of tubulin polymerization.</p><p><strong>Results: </strong>Derivative 6c displayed the best anticancer activity among the tested series while 6d was the best against breast cancer MDA-MB-468, therefore both of them were selected for the 5-dose stage, however, targeting MDA-MB-468, PI-flow cytometry of compound 6d proved the triggered cell growth arrest at the G1/S phase avoiding the mitotic cycle in MDA-MB-468 cells. Similarly, the upregulation of oncogenic parameters such as caspase-3, p53, and Bax/Bcl-2, along with the inhibition of PARP-1 enzyme level, was observed with compound 6d. This compound also exhibited a significant ability to induce apoptosis and disrupt the intracellular microtubule network through a promising activity as a tubulin polymerization inhibitor with IC₅₀ = 1.065 ± 0.024 ng/ml. Furthermore, to examine the manner in which compound 6d binds to the active pocket of the tubulin polymerization enzyme, a molecular docking study was conducted.</p><p><strong>Conclusion: </strong>The study indicated that compound 6d could be a powerful microtubule-destabilizing agent. Therefore, further research on 6d could be worthwhile.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"544-557"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Combinatorial Regimen Using Sorafenib and Uttroside B, A US FDA-designated 'Orphan Drug', for the Treatment of Hepatocellular Carcinoma.","authors":"Chenicheri Kizhakkeveettil Keerthana, Sreekumar U Aiswarya, Tennyson P Rayginia, Yadu Vijayan, Shirly James, Sadiq C Shifana, Sankar Sundaram, D K Induja, Ravi S Lankalapalli, Kuzhuvelil B Harikumar, Ruby John Anto","doi":"10.2174/0118715206316190240527160242","DOIUrl":"10.2174/0118715206316190240527160242","url":null,"abstract":"<p><strong>Introduction: </strong>Sorafenib (Sor) is the first-line treatment option in clinics for treating advanced unresectable hepatocellular carcinoma (HCC). However, acquired chemoresistance and adverse side effects associated with Sor monotherapy limit its clinical benefits. We have previously reported the exceptional anti-HCC potential of uttroside B (Utt-B), a furostanol saponin isolated in our lab from <i>Solanum nigrum</i> Linn. leaves. The current study has evaluated the supremacy of a combinatorial regimen of Sor and Utt-B over Sor monotherapy.</p><p><strong>Methods: </strong>MTT assay was used for <i>In vitro</i> cytotoxicity studies. A clonogenic assay was conducted to assess the anti-proliferative effect of the combination. Annexin V/PI staining, confocal microscopy, FACS cell cycle analysis, and Western blotting experiments were performed to validate the pro-apoptotic potential of the combination in HepG2 and Huh7 cell lines. Pharmacological safety evaluation was performed in Swiss albino mice.</p><p><strong>Results: </strong>Our results indicate that Utt-B augments Sor-induced cytotoxicity in HepG2 and Huh7 cells. The combination inhibits the proliferation of liver cancer cells by inducing apoptosis through activation of the caspases 7 and 3, leading to PARP cleavage. Furthermore, the combination does not induce any acute toxicity <i>in vivo</i>, even at a dose five times that of the effective therapeutic dose.</p><p><strong>Conclusion: </strong>Our results highlight the potential of Utt-B as an effective chemosensitizer, which can augment the efficacy of Sor against HCC and circumvent Sor-induced toxic side effects. Moreover, this is the first and only report to date on the chemosensitizing potential of Utt-B and the only report that demonstrates the therapeutic efficacy and pharmacological safety of a novel combinatorial regimen involving Utt-B and Sor for combating HCC.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"1431-1441"},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141915959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenoside Rb1 Inhibits the Proliferation of Lung Cancer Cells by Inducing the Mitochondrial-mediated Apoptosis Pathway.","authors":"Lin Feng, Xinze Liu, Kaijing Sun, Ying Sun, Wei Wu, Changbao Chen, Xin Jin, Xilin Wan","doi":"10.2174/0118715206299212240304142047","DOIUrl":"10.2174/0118715206299212240304142047","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is one of the more common malignant tumors posing a great threat to human life, and it is very urgent to find safe and effective therapeutic drugs. The antitumor effect of ginsenosides has been reported to be a treatment with a strong effect and a high safety profile.</p><p><strong>Objective: </strong>This paper aimed to investigate the inhibitory effect of ginsenoside Rb1 on 95D and NCI-H460 lung cancer cells and its pathway to promote apoptosis.</p><p><strong>Methods: </strong>We performed the CCK-8 assay, fluorescence staining assay, flow cytometry, scratch healing assay, and Transwell assay to detect the effects of different concentrations of ginsenoside Rb1 on the antitumor activity of 95D and NCI-H460 cells and Western Blot detected the mechanism of antitumor effect.</p><p><strong>Results: </strong>Ginsenoside Rb1 treatment significantly increased the inhibition and apoptosis rates of 95D and NCIH460 cells and inhibited the cell cycle transition from S phase to G2/M. Rb1 induces apoptosis by altering the levels of P53, Bax, Cyto-c, Caspase-8, Caspase-3, Cleaved Caspase-3, Bcl-2, MMP-2, and MMP-9 proteins and activating the external apoptotic pathway.</p><p><strong>Conclusion: </strong>Ginsenoside Rb1 inhibits proliferation and migration and induces apoptosis of 95D and NCI-H460 lung cancer cells by regulating the mitochondrial apoptotic pathway to achieve antitumor activity.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"928-941"},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140093359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bee Venom Toxic Effect on MDA-MB-231 Breast Cancer Cells and <i>Caenorhabditis Elegans</i>.","authors":"Yáskara Veruska Ribeiro Barros, Amanda Onduras de Andrade, Larissa Pereira Dantas da Silva, Lucas Aleixo Leal Pedroza, Iverson Conrado Bezerra, Iago Dillion Lima Cavalcanti, Mariane Cajuba de Britto Lira Nogueira, Kristiana Cerqueira Mousinho, Angelo Roberto Antoniolli, Luiz Carlos Alves, José Luiz de Lima Filho, Alexandre Varão Moura, Álex Aparecido Rosini Silva, Andréia de Melo Porcari, Priscila Gubert","doi":"10.2174/0118715206291634240312062957","DOIUrl":"10.2174/0118715206291634240312062957","url":null,"abstract":"<p><strong>Introduction: </strong>Bee venom has therapeutics and pharmacological properties. Further toxicological studies on animal models are necessary due to the severe allergic reactions caused by this product.</p><p><strong>Method: </strong>Here, <i>Caenorhabditis elegans</i> was used as an <i>in vivo</i> toxicity model, while breast cancer cells were used to evaluate the pharmacological benefits. The bee venom utilized in this research was collected from <i>Apis mellifera</i> species found in Northeast Brazil. The cytotoxicity caused by bee venom was measured by MTT assay on MDA-MB-231 and J774 A.1 cells during 24 - 72 hours of exposure. <i>C. elegans</i> at the L4 larval stage were exposed for three hours to M9 buffer or bee venom. Survival, behavioral parameters, reproduction, DAF-16 transcription factor translocation, the expression of superoxide dismutase (SOD), and metabolomics were analyzed. Bee venom suppressed the growth of MDA-MB-231 cancer cells and exhibited cytotoxic effects on macrophages. Also, decreased <i>C. elegans</i> survival impacted its behaviors by decreasing <i>C. elegans</i> feeding behavior, movement, and reproduction.</p><p><strong>Results: </strong>Bee venom did not increase the expression of SOD-3, but it enhanced DAF-16 translocation from the cytoplasm to the nucleus. <i>C. elegans</i> metabolites differed after bee venom exposure, primarily related to aminoacyl- tRNA biosynthesis, glycine, serine and threonine metabolism, and sphingolipid and purine metabolic pathways. Our findings indicate that exposure to bee venom resulted in harmful effects on the cells and animal models examined.</p><p><strong>Conclusion: </strong>Thus, due to its potential toxic effect and induction of allergic reactions, using bee venom as a therapeutic approach has been limited. The development of controlled-release drug strategies to improve this natural product's efficacy and safety should be intensified.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"798-811"},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140157386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperoxic-hypoxic Paradox: Breast Cancer Microenvironment and an Innovative Treatment Strategy.","authors":"Suman Kumar Ray, Sukhes Mukherjee","doi":"10.2174/0118715206290816240220062545","DOIUrl":"10.2174/0118715206290816240220062545","url":null,"abstract":"<p><p>A small therapeutic range of oxygen is required for effective metabolism. As a result, hypoxia (low oxygen concentration) is one of the most potent inducers of gene expression, metabolic alterations, and regenerative processes, such as angiogenesis, stem cell proliferation, migration, and differentiation. The cellular response is controlled by sensing the increased oxygen levels (hyperoxia) or hypoxia via specific chemoreceptor cells. Surprisingly, changes in free oxygen concentration instead of absolute oxygen levels may be regarded as a deficiency of oxygen at the cellular level. Recurrent intermittent hyperoxia may trigger many mediators of cellular pathways typically generated during hypoxia. The dilemma of hyperoxic-hypoxic conditions is known as the hyperoxic-hypoxic paradox. According to the latest data, the hypoxic microenvironment, crucial during cancer formation, has been demonstrated to play a key role in regulating breast cancer growth and metastasis. Hypoxic circumstances cause breast cancer cells to respond in a variety of ways. Transcription factors are identified as hypoxia-inducible factors (HIFs) that have been suggested to be a factor in the pathobiology of breast cancer and a possible therapeutic target, driving the cellular response to hypoxia. Breast cancer has a dismal prognosis due to a high level of resistance to practically all well-known cancer management that has been related to hypoxia-based interactions between tumor cells and the stromal milieu. We attempt to review the enigma by exploring the starring roles of HIFs in breast cancer, the HIF paradox, and the hyperoxic-hypoxic enigma.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"729-732"},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139982200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}